Expression of macrophage inflammatory protein-3 beta/CCL19 in pulmonary sarcoidosis

Am J Respir Crit Care Med. 2003 Jun 15;167(12):1695-703. doi: 10.1164/rccm.200205-487OC. Epub 2003 Mar 5.

Abstract

In this study, messenger RNA (mRNA) expression for novel T lymphocyte chemoattractants, leukotactin-1, macrophage inflammatory protein (MIP)-3 alpha and MIP-3 beta was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3 beta mRNA was upregulated in sarcoidosis, and therefore, protein levels of this chemokine, its pharmacologic regulation, and association with disease clinical course were explored. MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003). MIP-3 beta protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T cell subsets. mRNA expression for the MIP-3 beta receptor, CC chemokine receptor 7, was increased in sarcoidosis and correlated with MIP-3 beta protein levels. MIP-3 beta mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-3 beta is implicated in T lymphocyte recruitment in sarcoidosis, is associated with disease progression, and is downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiologic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Case-Control Studies
  • Chemokine CCL19
  • Chemokine CCL20
  • Chemokines, CC / analysis*
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology
  • Cyclosporine / immunology
  • Cyclosporine / therapeutic use
  • Dexamethasone / immunology
  • Dexamethasone / therapeutic use
  • Disease Progression
  • Down-Regulation / drug effects
  • Female
  • Gene Expression* / drug effects
  • Gene Expression* / genetics
  • Gene Expression* / immunology
  • Humans
  • Immunohistochemistry
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Macrophage Inflammatory Proteins / analysis
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / immunology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptors, CCR6
  • Receptors, Chemokine*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoidosis, Pulmonary / blood
  • Sarcoidosis, Pulmonary / drug therapy
  • Sarcoidosis, Pulmonary / immunology
  • Sarcoidosis, Pulmonary / pathology*
  • Severity of Illness Index
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • CCL19 protein, human
  • CCL20 protein, human
  • CCR6 protein, human
  • Chemokine CCL19
  • Chemokine CCL20
  • Chemokines, CC
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Receptors, CCR6
  • Receptors, Chemokine
  • Dexamethasone
  • Cyclosporine